Nucleosides, Nucleotides & Nucleic Acids最新文献

The relationship between TMEM132D and depressive symptoms in community populations has not been investigated. Therefore, we explored the association between TMEM132D gene polymorphism and depressive symptoms based on data from a community sample of older adults in Qingdao. A total of 863 older adults were included in this study to examine the relationship between 12 SNPs and depressive symptoms. Depressive symptoms were assessed using the Patient Health Questionnaire-9. Logistic regression analysis was used to analyze the relationship between SNPs and depressive symptoms based on five genetic models. Finally, linkage disequilibrium analysis was performed, and haplotype domains were constructed. We discovered a statistically significant difference between groups with and without depressive symptoms in the genotype and allele frequencies of rs2292723. In addition, multivariate logistic regression showed that rs2292723 and rs2170820 were positively associated with depressive symptoms, and rs61944776 was negatively associated with depressive symptoms. Finally, we found that the haplotype "CTC" of rs2292723, rs492759, and rs61944776 was significantly associated with depressive symptoms by haplotype analysis. Our study suggested that TMEM132D was associated with depressive symptoms, which supplemented the role of the TMEM132D gene in psychiatric disorders.

Epigenetic modifications play a crucial role in various diseases, including cancer. Targeting chromatin modulators to normalize these epigenetic markers is a promising avenue for overcoming cancer drug resistance and improving treatment efficacy. Histone chaperones, implicated in cancer due to their imperfect compensatory mechanisms, represent potential targets for epidrugs. To identify these targets, we performed enrichment and network analyses of histone chaperone interactions, both among themselves and with other proteins. This approach provided insights into structure-function relationships. The selective binding of histone chaperones to canonical histones highlights their potential as epidrugs targets. Network analysis of common histone chaperones identified key hub proteins: HSP90AB1, RBBP4, NPM1, DAXX, and SET. These hub proteins, particularly RBBP4, which formed the largest protein cluster was found associated with oncogenesis, suggesting RBBP4 as prime candidates for therapeutic intervention. Druggability prediction of these hub protein pockets further identified RBBP4 as the most promising target, with Ritonavir emerging as a potential epidrugs. These findings provide a crucial foundation for future epidrugs discovery targeting cancer.

Gene therapy has revolutionized the concept of treating genetic disorders by addressing the root causes at the genetic level, becoming one of the most quickly evolving fields in medicine today, especially due to its long-term effects. Gene therapy for the treatment of diseases relies on strategies of gene suppression, overexpression, and editing using different tools such as CRISPR and RNA interference. The gene transfer methods are broadly classified into three categories: physical, chemical, and biological. The use of viral vectors, such as adenoviruses, retroviruses, and adeno-associated viruses, is prevalent in clinical settings due to their high efficiency. Safety remains as an issue, and risk mitigation strategies will continue to evolve from clinical data to minimize complications related to gene silencing and immunotoxicity. In this review, various aspects of gene therapy have been covered, such as in-vivo and ex-vivo gene therapy, gene transfer methods, safety issues, as well as the gene therapy products approved until 2022. This review lists 35 licensed gene therapy products, detailing their therapeutic uses, mechanism of action, and vectors employed. Each product illustrates the various applications and potentials of gene therapy against untreatable conditions. Continuous improvements in gene transfer methods, vector safety, and clinical applications will increase the impact of the technology and offer hope for effective treatment and possible cures for different genetic disorders.

Colon cancer ranks among the prevalent malignancies globally, and its proclivity for metastasis significantly contributes to the adverse prognostic outcomes observed in patients. The epithelial-mesenchymal transition (EMT) represents a critical biological process through which tumor cells gain migratory and invasive capabilities. Nilotinib is a selective inhibitor of tyrosine kinases, commonly utilized in the treatment of chronic myeloid leukemia. Prior investigations have demonstrated that the Nilotinib derivative, N-12, exhibits significant antitumor properties. The objective of this study is to elucidate the inhibitory effects of N-12 on the progression of EMT in colon cancer cells. So, the human colon cancer cell line HCT116 and SW480 were selected for experimentation. Initially, assessments of cell proliferation, migration and invasion were conducted utilizing MTT, colony formation, Edu and Transwell assays. Subsequently, the chick embryo chorioallantoic membrane model was employed to evaluate tumor size and its impact on angiogenesis in vivo. Thereafter, HCT116 cells treated with N-12 underwent RNA sequencing for analysis. Finally, the expression levels of EMT markers in colon cancer cells were determined by Western blot analysis. The results showed that N-12 significantly curtails the proliferation, migration, and invasion of colon cancer cells, and concurrently impedes tumor growth in vivo by influencing angiogenesis within the chick embryo chorioallantoic membrane. Furthermore, RNA sequencing and Western blot analyses have elucidated that the antitumor efficacy of N-12 is attributable to the inhibition of the EMT signaling pathway. These results underscore the therapeutic potential of N-12 in the management of colon cancer and delineate its mechanism of action.

In the early stages, chronic kidney disease (CKD) can be asymptomatic, marking diagnosis difficult. This study aimed to investigate the diagnostic role and potential regulatory mechanisms of nucleolar protein 14 (NOP14) -antisense RNA 1 (AS1) in patients with CKD. Herein, 68 patients with CKD, 65 patients with CKD undergoing peridialysis, and 80 healthy adults were included. The real-time reverse transcription-quantitative polymerase chain reaction was performed to assess NOP14-AS1 levels, and its diagnostic value was evaluated using receiver operating characteristic curves. Additionally, cell proliferation and apoptosis were assessed by Cell Counting Kit-8 assay. and flow cytometry, respectively. Oxidative stress levels were determined using superoxide dismutase and malondialdehyde MDA kits, and the dual-luciferase reporter assay was performed to determine the relationship between NOP14-AS1 and microRNA-326 (miR-326) target binding. Lastly, the potential mechanism underlying miR-326 target gene regulation in CKD progression were explored utilizing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Notably, patients with CKD exhibited decreasedNOP14-AS1 levels and upregulated miR-326 levels. NOP14-AS1 and miR-326 exhibited combined effects on cell proliferation, apoptosis, inflammatory factors, and oxidative stress levels. Furthermore, the target genes of miR-326 showed enrichment in CKD-associated rat sarcoma and phosphoinositide 3-kinase protein kinase B pathways. Altogether, the findings of this study show the potential of NOP14-AS1 as a diagnostic marker in CKD. Overall, NOP14-AS1 regulates the miR-326 expression, which, in turn, regulates various miR-326 target gene-associated signaling pathways, thereby affecting the occurrence and development of CKD.

Genes involved in lipid metabolism have been considered potential therapeutic targets in lung cancer because lipid metabolism is severely disrupted in this cancer. Monoglyceride lipase (MGLL) is a lipolytic enzyme that converts monoacylglycerides to fatty acids and glycerol. MicroRNAs (miRNA), one of the most important epigenetic regulators of gene expression, are also considered potential biomarkers in diagnosing, treating, and prognosis lung cancer. This study aimed to investigate the potential effects of MGLL and related miRNAs (miR-302b-5p, miR-190a-3p, miR-450a-2-3p) in the pathogenesis of non-small cell lung cancer (NSCLC) by examining their expression levels and regulatory mechanisms. We analysed the expression levels of MGLL and miRNAs in 30 NSCLC and 20 non-cancerous tissues by qPCR. We performed in silico analyses to determine the biological functions of MGLL and miRNAs in NSCLC. A protein-protein interaction (PPI) network was constructed for MGLL, and gene ontology (GO) analysis, and the interacting genes were analysed using the TCGAnalyzer tool. Our study showed that the expression levels of MGLL, miR-302b-5p, miR-190a-3p and miR-450a-2-3p were significantly decreased in NSCLC tissues (p < 0.05). Also, according to TCGAnalyzer, MSRB3, HTR4, and FCER1G genes were downregulated genes for NSCLC. We showed that miR-302b-5p, miR-190a-3p, and miR-450a-2-3p significantly regulate the TGF-β signalling pathway. In conclusion, this study provides evidence for the potential role of MGLL and microRNAs (miR-302b-5p, miR-190a-3p, miR-450a-2-3p) in NSCLC. In subsequent studies, it was determined that MSRB3, FCER1G and LTB4R2 genes, especially the HTR4 gene, could be potential target genes for lung cancer.

PIWI-Interacting RNAs are small non-coding RNAs derived from single-stranded RNAs which plays a crucial role in epigenetic regulation through transposon silencing and mRNA degradation via deamination. This study aimed to inhibit piR-651 and piR-823 in MDA-MB-231 triple-negative breast cancer cells and to explore their potential effects on healthy HUVEC cells. Non-target, anti-piR-651, and anti-piR-823 sequences were transfected in bothHUVEC and MDA-MB-231 cells using Lipofectamine. Proliferation and motility were assessed at 24, 48, and 72 h post-transfection in both cell lines. Based on the motility findings, MDA-MB-231 cells were underwent an invasion assay using crystal violet staining. The expressions of Ki-67, HIF-1α, MMP-2, and MMP-9 genes were measured at 48 h, when both cell lines exhibited the most significant effects of inhibition. The optimal time for proliferation of anti-piR-651 and anti-piR-823 transfected MDA-MB-231 cells was determined to be at 48 h, as indicated by decreased motility and invasion assay results (p < 0.001). NeverthelessHowever, there was no significant difference in the motility and proliferation of HUVECss transfected with anti-piR-651 and anti-piR-823 compared to the control group (p > 0.05). Asides from MMP-2 in anti-piR-823 transfected HUVECs and HIF-1α in anti-piR-823 transfected MDA-MB-231 cells, gene expressions of Ki-67, HIF-1α, MMP-2, and MMP-9 were reduced in both cell lines (p < 0.001). Inhibition of piR-651 and piR-823 decreased the survival and metastasis of cancer cells, without causing vital structural changes in healthy cells. Future research in cancer gene therapy or genetic modification may benefit from investigating piR-651 and piR-823 as possible inhibitors of breast cancer invasion and metastasis.

Murine maternal obesity predisposes offspring to obesity and other non-communicable diseases. Fetal programming enables researchers to trace this detrimental effect in the early life of the offspring. The aim of the current study was to explore the molecular impact of maternal obesity on the livers of murine offspring at weaning age. C57BL/6 female mice were exposed to a high-fat diet to induce obesity, after which they were mated to produce offspring. At weaning age, the metabolic health of female offspring was assessed and hepatic mRNAs were investigated via mRNA high throughput sequencing. The differentially expressed genes were identified using gene and protein expression analyses. The results revealed that murine maternal obesity altered the blood parameters, liver histology and gene expression of offspring. Cyclin-dependent kinase 1 (Cdk1) and E2f transcription factor 1 (E2f1) were identified as hub genes by bioinformatics analysis. Reverse transcription-quantitative PCR, western blotting and immunohistochemical analysis all revealed that the expression of Cdk1 and E2f1 was decreased in the livers of offspring born from obese does. In conclusion, murine maternal obesity impaired lipid metabolism in the livers of their offspring at weaning age. Furthermore, Cdk1 and E2f1 were identified as hub genes in the regulatory mechanism.

Background: Genetic factors play a crucial role in the development of major depressive disorder (MDD).

Objectives: This study aimed to investigate the association between the microRNA (miR)-34a rs266643 polymorphism and MDD, as well as its impact on cognitive function.

Materials and methods: Clinical data and blood samples were collected from 302 MDD patients and 306 healthy controls who met the predefined inclusion and exclusion criteria. The severity of MDD in patients was assessed using the Hamilton Rating Scale for Depression (HRSD). Cognitive function in MDD patients was evaluated using the Mini-Mental State Examination (MMSE), Stroop Color-Word Test (Stroop-C and Stroop-CW), and Montreal Cognitive Assessment (MoCA). Gene typing was performed using the Sanger sequencing method, while the relative expression level of miR-34a was quantified by RT-qPCR.

Results: The MDD group exhibited a significantly higher miR-34a expression fold change compared to the control group (p < 0.001). Among the genotypes, the AA genotype demonstrated the highest expression, followed by GA, with both being significantly greater than GG. The expression of miR-34a was positively correlated with HRSD, Stroop-C, and Stroop-CW scores but negatively correlated with MMSE and MoCA scores (p < 0.001). Carrying the A allele (OR = 1.468, p = 0.002) or the AA genotype (OR = 2.382, p = 0.001) was associated with an increased risk of MDD. Furthermore, patients with the AA genotype exhibited significantly poorer cognitive function compared to other genotypes.

Conclusion: The gene polymorphism of miR-34a rs2666433 was significantly associated with the severity of MDD as well as cognitive function.

The first structure of a boronic acid-modified nucleoside is elucidated by single-crystal X-ray diffraction and compared to its tert-butyldimethylsilyl-protected nucleoside derivative. Further, we present the synthetic access to boronic acid-modified -nucleosides providing alternative reaction conditions to a reported synthesis. Although the sugar pucker of the boronic acid-modified nucleoside differs slightly from other nucleosides, the geometry around the nucleobase shows a high degree of structural similarity to the nucleosides of the natural nucleobases. Inter- as well as intramolecular hydrogen bonds are present involving the boronic acid residue as donor. The interconnection via hydrogen bonds permits the formation of suprastructures in form of linear zigzag chains in the solid state. In conclusion, the structural influence by the boronic acid residue on the overall nucleoside's geometry was only minor which favours its potential use as functionalised thymidine analogue in deoxyoligonucleotides.